1. Technical Field
The present invention relates generally to the field of devices for measuring the osmolarity of a relatively small volume of fluid, and in particular to a method and an apparatus for measuring, in vivo, the osmolarity of human tears.
2. Related Art
Dry eye syndrome (DES), a condition that occurs due to loss of water from the tear film, is one of the most common complaints seen by optometrists. Studies have found that DES is common in about 15% of patients over the age of 50, with prevalence increasing with age. Dry eye in general is caused by any condition that increases tear film evaporation, or by any condition that decreases tear production. For some patients, evaporation is increased as a result of having larger eyes. Larger eyes cause greater evaporation due to the larger surface area and the loss of water. Tear production can also decrease from any condition that decreases corneal sensation. Long-term contact lens wear, LASIK eye surgery, trauma to the 5th nerve, and certain viral infections cause decrease in corneal sensation. The treatment of DES depends on the severity of the condition. Some patients find relief from DES through the use of various artificial tears available on the market. Additionally, some patients are prescribed Omega-3 containing supplements. There are cases where “punctual plugs” need to be inserted to stop drainage of tears.
Osmolarity is the measure of the concentration of osmotically active particles in a solution, which may be quantitatively expressed in osmoles of solute per liter of solution. It is known that when the tear film loses water, salt and protein concentrations increase relative to the amount of water. When the concentration of salt and protein increases relative to the amount of water, osmolarity increases. Therefore, in order to diagnose and treat DES patients, it is desirable for a treating physician to quantify the osmolarity of a sample tear fluid. Some current osmolarity measurement methods and devices available include: osmotic pressure measurement, freezing point measurement, and vapor pressure measurement.
In one approach, an osmometer is used to measure the osmotic pressure exerted by a solution across a semi-permeable membrane. In this approach, a solvent and solution are separated by the semi-permeable membrane, which allows only solvent molecules to pass through. The osmotic pressure of the solution can be determined by measuring the excess pressure that must be applied to the solution to prevent the solvent from passing into the solution.
In another approach, the osmolarity of a sample fluid (e.g., a tear) can be determined by an ex vivo technique called “freezing point depression.” In this technique, solutes or ions in a solvent (i.e., water) cause a lowering of the fluid freezing point from what it would be without the ions. In the freezing point depression analysis, the freezing point of the ionized sample fluid is found by detecting the temperature at which a quantity of the sample (typically on the order of about several milliliters) first begins to freeze in a container (e.g., a tube). To measure the freezing point, a volume of the sample fluid is collected into a container, such as a tube. Next, a temperature probe is immersed in the sample fluid, and the container is brought into contact with a freezing bath or Peltier cooling device. The sample is continuously stirred so as to achieve a supercooled liquid state below its freezing point. Upon mechanical induction, the sample solidifies, rising to its freezing point due to the thermodynamic heat of fusion. Deviation of the sample freezing point from 0 degrees C. is proportional to the solute level in the sample fluid (i.e., osmolarity value).
Another ex vivo technique for osmolarity testing measures vapor pressure. In this method, a small, circular piece of filter paper is lodged underneath a patient's eyelid until sufficient fluid is absorbed. The filter paper disc is placed into a sealed chamber, whereupon a cooled temperature sensor measures the condensation of vapor on its surface. Eventually the temperature sensor is raised to the dew point of the sample. The reduction in dew point proportional to water is then converted into osmolarity. However, because of induced reflex tearing, osmolarity readings are not as accurate. Similarly, in vivo techniques, which attempt to measure osmolarity by placing electrodes directly under the eyelid of a patient, are likely to induce reflex tearing. As a result the above-described approaches are neither convenient nor accurate for an eye doctor operating in a clinical environment.
There is a need for a clinically feasible, nanoliter-scale osmolarity measurement device, with the capability for reduced evaporation, that does not suffer from the problems of the related art.